Cardiac arrhythmias represent a diverse set of conditions characterized by abnormal electrical activity in the heart, resulting in heart rates that are too fast, too slow, or irregular. The most common sustained and clinically significant cardiac arrhythmia is atrial fibrillation (AF). AF is caused by disorganized electrical impulses originating in the atria and pulmonary veins that propogate as irregular electrical signals to the ventricals, resulting in irregular heart rates. AF is frequently associated with symptoms such as palpitations, shortness of breath, fatigue, chest pain and loss of consciousness. AF is a major risk factor for stroke and other embolic events, as it predisposes to the formation of clots in the left atrial appendage, due to the pooling of blood resulting from the inefficient contraction of the atria. The risk of developing AF increases with age, with one in four individuals expected to develop AF during their lifetime. AF currently affects over 2 million Americans, and is expected to affect over 5 million individuals by the year 2050.
AF is frequently associated with conditions such as hypertension, diabetes, valvular heart disease and congestive heart failure (CHF). In fact, up to half of all patients with CHF have concomitant AF. AF is also known to commonly occur after open-heart surgery. The incidence of AF in the perioperative setting is estimated to be around 30% with nearly 50% of patients experiencing AF following valve surgery. Postoperative AF is associated with prolongation in the length of hospitalization, cost of surgery, need for mechanical ventilation, pacemaker requirement, stroke, and possibly death. The economic impact of this disease has been estimated at $6.6 billion. The diagnosis and management of AF have therefore become important and challenging aspects of cardiovascular medicine.
Current treatments for atrial fibrillation include pharmacologic and non-pharmacologic strategies. Pharmacologic strategies for treatment of atrial fibrillation are group into four classes: Class 1: sodium channel blockers, which decrease the rate of electrical conduction in cardiac muscle; Class 2: beta-adrenergic receptor blockers (beta blockers), which decrease the rate of conduction through the heart and thus render the AV node less sensitive to the disorganized electrical signals; Class 3: potassium channel blockers, which slow nerve impulses in the heart muscle, and; Class 4: calcium channel blockers, which impede cardiac muscle cell contraction, allowing blood vessels to expand which increases the oxygenation of cardiac tissue. In addition to treating the underlying atrial fibrillation, patients are routinely treated with blood thinning agents such as aspirin, warfarin, clopidogrel, and ticlopidine to reduce the risk of stroke. Non-pharmacologic treatments include electrical cardioversion and implantation of atrial pacemakers. Recent years have seen the development of more ‘curative’ techniques such as catheter ablation and surgical Maze procedures. However, these procedures have high efficacy only in selected patient groups, and can be associated with significant complications. In view of the limitations of these empiric ablation/surgical approaches, recent research efforts have attempted to develop novel therapies that target specific mechanisms involved in the genesis of AF.
The autonomic nervous system has been implicated as a major contributor to the genesis and maintenance of focal atrial fibrillation. Recent clinical studies suggest that an alteration of vagal input to the posterior left atrium and the pulmonary veins, as measured by the elimination of vagal reflexes on pulmonary vein stimulation, may improve efficacy of ablation procedures for atrial fibrillation. Recent studies suggest a dominant role for the parasympathetic nervous system in atrial fibrillation, with the sympathetic nervous system playing an important modulatory role in the genesis of this arrhythmia. In the setting of CHF, blocking the sympathetic nervous system changes the characteristics of AF, without significantly affecting the maintenance of AF; these data further support a more modulatory role for the sympathetic nervous system in the creation of AF substrate.